1. Field of the Invention
This invention relates to a crystallization method for polymorphic glutamic acid crystals which preferentially produces metastable α-form crystals.
2. Brief Description of the Related Art
Glutamic acid crystals are polymorphic, that is, two forms exist of these crystals. One form is an α-form which is metastable, and the other is a β-form which is stable.
The existence of α-form crystals has been known for a long time (JP36-017712B). Methods are also known for purifying glutamic acid by first precipating the α-form crystals, and then converting them to β-form crystals (JP45-004730B). This conversion is thought to occur due to impurities in α-form crystals that are released.
To produce α-form crystals, it has been reported that a supersaturated state can be achieved by adding an acid to a glutamic acid salt solution, resulting in a decrease in solubility of glutamic acid. Then, α-form crystals can be added as seed crystals. This method is similar to a methods employed for producing glycine crystals, wherein α-form crystals are added (N. Doki et al., Crystal Growth & Design, 4(5), 949-953, 2004). α-form crystals can also be produced by adding amino acids or sugars (JP36-017712B, JP45-011286B). In addition, it is known that α-form crystals are precipitated first upon reaching supersaturation, and then the crystals can stand without adding seed crystals (Jochen Scholl et al., Chem. Eng. Technol. 29(2), 257-264, 2006). However, a crystallization method of preferentially producing only α-form crystals by utilizing this phenomenon has not been reported.
Incidentally, the conventional method of producing α-form crystals by adding seed crystals has several problems. For example, it is difficult to store prepared seed crystals so that they do not convert to β-form crystals, due to moisture which adheres to the separated crystals. Also, it is difficult to control a glutamic acid salt solution to a particular rate of supersaturation, because in the range of pH 4-6, solubility of glutamic acid is highly sensitive to changes in pH. That is, when adjusting the pH, and the pH becomes lower than desired due to adding the acid too quickly, stable β-form crystals will precipitate due to the high rate of achieving supersaturation. Whereas, when the pH becomes too high, the added seed crystals are dissolved, and accordingly, the seed crystals are not effective at all, which also results in the precipitation of β-form crystals.
Finally, producing α-form crystals by adding amino acids or sugars results in the addition of impurities to the system, and accordingly, it does not meet the objectives of purification wherein the removal of impurities is a primary function of crystallization.